Selective delivery of insulin into the brain: Intraolfactory absorption

被引:15
作者
Gizurarson, S [1 ]
Thorvaldsson, T [1 ]
Sigurdsson, P [1 ]
Gunnarsson, E [1 ]
机构
[1] UNIV ICELAND,INST EXPT PATHOL,IS-112 REYKJAVIK,ICELAND
关键词
D O I
10.1016/0378-5173(96)04579-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The distribution of insulin between blood and brain was investigated in mice. The drug was administered subcutaneously and by instilling the drug to the olfactory region of the nasal cavity. The concentrations of insulin in the biological samples were measured by a gamma-counter. A significantly higher concentration of insulin was measured in the brain, following intraolfactory administration compared to subcutaneous injection. The absorption was also found to be very rapid. Ten minutes after the administration the concentration in the brain had reached 193 counts/min per g (equivalent to 37 mu U insulin/g tissue), which was 487% higher than achieved after subcutaneous injection. The majority (>99%) of the CNS drug development programmes are devoted solely to CNS drug discovery and less than 1% are devoted to drug delivery. The results suggest that it may be possible to achieve absorption directly into the brain, by-passing the blood-brain barrier. The olfactory region may be the key for this absorption.
引用
收藏
页码:77 / 83
页数:7
相关论文
共 20 条
[1]   INSULIN AND INSULIN-LIKE GROWTH-FACTORS IN THE CNS [J].
BASKIN, DG ;
WILCOX, BJ ;
FIGLEWICZ, DP ;
DORSA, DM .
TRENDS IN NEUROSCIENCES, 1988, 11 (03) :107-111
[2]   SATURABLE TRANSPORT OF INSULIN FROM PLASMA INTO THE CENTRAL-NERVOUS-SYSTEM OF DOGS IN-VIVO - A MECHANISM FOR REGULATED INSULIN DELIVERY TO THE BRAIN [J].
BAURA, GD ;
FOSTER, DM ;
PORTE, D ;
KAHN, SE ;
BERGMAN, RN ;
COBELLI, C ;
SCHWARTZ, MW .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (04) :1824-1830
[4]   ACCUMULATION OF CD(II) IN THE CNS DEPENDING ON THE ROUTE OF ADMINISTRATION - INTRAPERITONEAL, INTRATRACHEAL, OR INTRANASAL [J].
EVANS, J ;
HASTINGS, L .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1992, 19 (02) :275-278
[5]   FINE-STRUCTURAL ASPECTS OF SECRETION AND EXTRINSIC INNERVATION IN THE OLFACTORY MUCOSA [J].
GETCHELL, ML ;
GETCHELL, TV .
MICROSCOPY RESEARCH AND TECHNIQUE, 1992, 23 (02) :111-127
[6]  
GIZURARSON S, 1991, CHEM PHARM BULL, V39, P2155
[7]   THE RELEVANCE OF NASAL PHYSIOLOGY TO THE DESIGN OF DRUG ABSORPTION STUDIES [J].
GIZURARSON, S .
ADVANCED DRUG DELIVERY REVIEWS, 1993, 11 (03) :329-347
[8]   INTRANASAL ADMINISTRATION OF INSULIN TO HUMANS [J].
GIZURARSON, S ;
BECHGAARD, E .
DIABETES RESEARCH AND CLINICAL PRACTICE, 1991, 12 (02) :71-84
[9]  
GIZURARSON S, 1995, SCAND J LAB ANIMAL S, V22, P273
[10]  
GIZURARSON S, UNPUB INT J PHARM